Abstract Core B The Imaging Core B (Paul Thompson, Director) provides brain image analysis for Projects 1-4, which analyze neurodegenerative responses to air pollution. Sub-core B1 (M. Braskie) supports Projects 1 and 2 on human brain MR images. Sub-core B2 (B. Zlokovic) supports Projects 3 and 4 on mouse brain. Sub-core B1 Human Neuroimaging Aim 1: Perform standardized structural image analyses in the ADNI, WHIMS and VETSA cohorts to assess voxelwise cortical thickness, volumes of selected Alzheimer's disease (AD)-relevant subcortical structures (hippocampus and amygdala), and regional white matter using FreeSurfer software. We will also assess white matter hyperintensity volumes. In ADNI and VETSA we will analyze diffusion tensor imaging scans. Aim 2: Use machine learning to generate structural MRI cortical signatures and associated predicted risk scores related to risk for preclinical AD, mild cognitive impairment, and AD. Aim 3: Support Projects 1 & 2 in their proposed mediation analyses using both targeted approach in structural equation models (SEM) and agnostic approach with high-dimensional analyses. Sub-Core B2, Mouse brain imaging. Aim 1. Perform in vivo mouse brain imaging to assess cerebral blood flow, blood brain barrier (BBB) permeability, vascular angiography, and MRI tractography. Aim 2. Postmortem studies of the neurovascular unit & BBB by confocal microscopy for immunofluorescence. Aim 3. Ultra-highfield MRI to detect mouse connectivity changes through diffusivity and tractography maps & quantification of BBB permeability by dynamic contrast enhanced (DCE)-MRI. Aim 4 Analyze mouse data from Projects 3 and 4.